The mitochondrial pyruvate dehydrogenase complex (mtPDC) catalyzes the decarboxylation of pyruvate yielding acetyl-CoA and NADH which are precursors of the Krebs cycle and oxidative phosphorylation. The mtPDC provides acetyl-CoA for the citrate synthase and acetyl-CoA hydrolase reactions and NADH for the electron transport system.
Pyruvate dehydrogenase complex (PDC) contains three primary component enzymes, pyruvate dehydrogenase (PDH, E1), dihydrolipoamide transacetylase (E2) and dihydrolipoamide dehydrogenase (E3).
The mtPDC provides a site for regulation due to its strategic metabolic location and the irreversible nature of the reaction. All PDCs exhibit product inhibition by acetyl-CoA and NADH. For mtPDCs, but not plastidial PDCs, reversible phosphorylation of the alpha subunit of E1 provides and "off-on" switch for mtPDC activity.
Reversible phosphorylation of PDC is catalyzed by two regulatory enzymes, PDH kinase (PDK) and P-PDH phosphatase. Both of these regulatory enzymes are specific for PDH.